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CC BY-NC-ND 4.0 · AJP Rep 2019; 09(02): e138-e143
DOI: 10.1055/s-0039-1683362
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice

Matthew R. Grace
1  Tennessee Maternal Fetal Medicine and the University of Tennessee, Division of Obstetrics and Gynecology, Department of Clinical Medicine Education, Nashville, Tennessee
,
Sarah K. Dotters-Katz
2  Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina
,
Chunxiao Zhou
3  Division of Gynecologic Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
,
Tracy Manuck
4  Division of Maternal–Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
5  Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology and Carolina Institute for Environmental Health Solutions, University of North Carolina School of Medicine, Chapel Hill, North Carolina
,
Kim Boggess
4  Division of Maternal–Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
,
Victoria Bae-Jump
3  Division of Gynecologic Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
› Author Affiliations
Further Information

Publication History

25 October 2018

11 December 2018

Publication Date:
09 April 2019 (online)

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Abstract

Objective This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice.

Study Design Pregnant friend virus B (FVB)-strain mice were allocated on embryonic day (e) 0.5 to one of four groups; group 1: control diet (CD, 10% fat) + control treatment (CT), group 2: CD + metformin treatment (MT), group 3: high-fat diet (HFD, 60% fat) + CT, and group 4: HFD + MT. Metformin (2.5 mg/mL) was provided in water; CT mice received water. Fetuses and placentas were collected. Western blot measured placental p-Akt and p-S6 expression.

Results 20 dams (five/group) and 192 fetuses were studied. Compared with CD-fed, HFD-fed dams had higher placental p-Akt protein expression (p < 0.0001). Among HFD-dams, placental p-Akt was higher in metformin-treated compared with control-treated (p < 0.001). Among CD-fed dams, there was no significant difference in placental p-S6 expression in MT versus CT groups. Among HFD-fed dams placental p-S6 expression was lower in those exposed to metformin-treated versus controls (p = 0.001).

Conclusion Increased placental mTOR signaling and metformin inhibition of placental mTOR signaling only occurred in the presence of an HFD exposure. These findings suggest that metformin may modulate placental mTOR signaling in the presence of metabolic exposures during pregnancy.

Keywords

metformin - mTOR - mice - high-fat diet

Presentation

Presented, in part, in poster format at the Society for Maternal Fetal Medicine's 37th Annual Pregnancy Meeting, January 27, 2017, Las Vegas, NV.


Financial Disclosure

This study was funded, in part, by the UNC Cefalo-Bowes Young Investigator Award (Dr. M.R.G.), the UNC Oliver Smithies Investigator Award (Dr. K.B.).